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Viral-induced inflammation is accompanied by β-amyloid plaque reduction in brains of amyloid precursor protein transgenic Tg2576 mice


Dr Tobias Stahl, as above.


Amyloid plaques, one of the neuropathological hallmarks of Alzheimer's disease, and their main constituent, the amyloid β-peptide (Aβ), are triggers of the activation of innate inflammatory mechanisms involving the activation of microglia. To dissect the effects of a non-Aβ-specific microglial activation on the Aβ metabolism, we employed a viral infection-based model. Transgenic mice expressing a mutated form of the human amyloid precursor protein (Tg2576) were used. In preceding experiments, 2-week-old transgenic mice and non-transgenic littermates were infected intracerebrally with the neurotropic Borna disease virus and investigated at 2, 4 and 14 weeks post-infection. The Borna disease virus-inoculated mice showed a persisting, subclinical infection of cortical and limbic brain areas characterized by slight T-cell infiltrates, expression of cytokines and a massive microglial activation in the hippocampus and neocortex. Viral-induced effects reached their peak at 4 weeks post-infection. In 14-month-old Tg2576 mice, characterized by the deposition of diffuse and dense-core amyloid plaques in cortical brain regions, Borna disease virus-induced microglial activation in the vicinity of Aβ deposits was used to investigate the influence of a local inflammatory response on these deposits. At 4 weeks post-infection, histometric analyses employing Aβ immunohistochemistry revealed a decrease of the cortical and hippocampal Aβ-immunopositive area. This overall decrease was accompanied by a decrease of parenchymal thioflavin-S-positive amyloid deposits and an increase of such deposits in the walls of cerebral vessels, which indicates that the elicitation of a non-Aβ-specific microglial activation may contribute to a reduction of Aβ in the brain parenchyma.